Centers for Disease Control and PreventionNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and PreventionNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and PreventionNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and PreventionNational Center for Immunization and Respiratory Diseases

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Pneumococcal Disease and Pneumococcal Vaccines

Andrew Kroger, M.D., M.P.H.Medical Educator

Pink Book Webinar SeriesSeptember 24, 2018

Streptococcus pneumoniae

Gram-positive bacteria

92 known serotypes

Polysaccharide capsule important virulence factor

Type-specific antibody is protective

Limited cross-reactivity

Second most common cause of vaccine-preventable death in the U.S.

Major clinical syndromes– Pneumonia– Bacteremia– Meningitis

Pneumococcal Disease

Invasive Pneumococcal DiseaseIncidence by Age Group–2013*

*CDC Active Bacterial Core surveillance 2009 report: http://www.cdc.gov/abcs/reports-findings/survreports/spneu13.html

0

5

10

15

20

25

30

35

<1 1 2-4 5-17 18-34 35-49 50-64 65+

Rate

/100

,000

pop

.

Age Group (Yrs)

Trends in Invasive Pneumococcal Disease Among Adults 19–64 Years of Age, 1998–2015

http://www.cdc.gov/abcs/reports-findings/survreports/spneu-types.html

Trends in Invasive Pneumococcal Disease Among Adults 65 Years of Age and Older, 1998–2015

http://www.cdc.gov/abcs/reports-findings/survreports/spneu-types.html

Functional or anatomic asplenia, including sickle-cell disease Altered immunocompetence Underlying medical conditions, including chronic renal disease,

nephrotic syndrome, and CSF leak Cigarette smoking (adults 19 years and older) Cochlear implant

Risk Factors for Invasive Pneumococcal Disease

Reservoir Human carriers

Transmission Respiratory and autoinoculation

Temporal pattern Winter and early spring

Communicability Unknown; probably as long as organism in respiratory secretions

Pneumococcal Disease Epidemiology

1977 14-valent polysaccharide vaccine licensed

1983 23-valent polysaccharide vaccine licensed (PPSV23)

2000 7-valent polysaccharide conjugate vaccine licensed (PCV7)

2010 13-valent polysaccharide conjugate vaccine licensed (PCV13)

Pneumococcal Vaccines

Purified capsular polysaccharide antigen from 23 types of pneumococcus

Not effective in children younger than 2 years

Pneumococcal Polysaccharide Vaccine (PPSV23) Characteristics

Contains 13 serotypes of S. pneumoniae conjugated to nontoxic diphtheria CRM197 carrier protein

Approval based on demonstration of immunologic noninferiority to PCV7 rather than clinical efficacy

Pneumococcal Conjugate Vaccine (PCV13) Characteristics

MMWR 2010;59(No. 9):258-61

PCV7 introduced into routine schedule 2000

PCV7 Introduction Among U.S. Children and its Impact on Invasive Pneumococcal Disease

Moore, IDSA, 2009 and CDC, unpublished data

0102030405060708090

100

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Case

s per

100

,000

Year

Rates of IPD Among Children <5 yrs old

Overall -76 (-79,-73)

PCV7 type -100 (-100,-99)

PCV7 Introduction

Pneumococcal Conjugate Vaccine (PCV13) in Children

In 2008, 61% of invasive pneumococcal disease cases among children younger than 5 years were attributable to the serotypes included in PCV13

In 2013, 20%-25% of invasive pneumococcal disease cases among adults 65 years old and older were attributable to PCV13 serotypes

10 percent of community-acquired pneumonia in adults due to PCV13 serotypes (Pfizer urine studies)

Pneumococcal Conjugate Vaccine (PCV13)in Adults

Most estimates range between 60%-70% effective against invasive disease among immunocompetent older persons and adults with underlying illnesses Effectiveness among immunocompromised or very old persons not

demonstrated

Pneumococcal Polysaccharide Vaccine (PPSV23)Immunogenicity/Effectiveness

Highly immunogenic in infants and young children, including those with high-risk medical conditions

PCV7 was 97% effective against invasive disease caused by vaccine serotypes (presumably PCV13 as well)

Pneumococcal Conjugate Vaccine (PCV13) Immunogenicity/Efficacy

New Evidence Supporting PCV13 use among Adults, CAPiTA Results

CAPiTA, ACIP, June 2014

Study/Population EndpointVaccine Efficacy

(95% CI)CAPiTA

~85,000 Adults 65+

Netherlands

PCV13-serotype IPD 75% (41%, 91%)

PCV13-serotype

nonbacteremicpneumonia

45% (14%, 65%)

PCV13 is approved by the Food and Drug Administration for: – Children 6 weeks through 17 years of age

– Adults 50 years of age and older

ACIP recommended use of PCV13 for immunocompromised persons 6 years and older (2012, 2013) ACIP recommended use of PCV13 for all adults 65 years or older in

2014

PCV13 Licensure

PCV13 in Children

Routine vaccination recommendation for children 2–59 months of age– 4 doses at 2, 4, 6, and 12 to 15 months– Fewer doses if series started at 7 months of age or older

Children who have received 1 or more doses of PCV7 should complete the immunization series with PCV13

ACIP Recommendations for PCV13

MMWR 2010;59(No. 9):258-61

Age at First Dose # of Doses Booster

7-11 months 2 doses Yes

12-23 months 2 doses* No

24-59 months 1 dose No

24-71 months, medical conditions** 2 doses* No

Pneumococcal Conjugate Vaccine Schedule for Unvaccinated Older Children–Primary Series

*Separated by at least 8 weeks; see MMWR2010;59(RR-11):1–19

**Chronic heart, lung disease, diabetes, CSF leak, cochlear implant, sickle cell disease, other hemoglobinopathies, functional or anatomic asplenia, HIV infection, immunocompromising conditions

A single supplemental dose of PCV13 is recommended for children who have received a complete age-appropriate series of PCV7:– Healthy children 14 through 59 months– Children 14 through 71 months with an underlying medical condition (including

those who have already received a dose of PPSV)

ACIP Recommendations for PCV13Supplemental Dose

MMWR 2010;59(No. 9):258-61

Children aged 24–71 months with underlying medical conditions who received an incomplete schedule of PCV7 should receive 2 doses of PCV13 (8 weeks apart)

ACIP Recommendations for PCV13Children

A dose of PCV13 should be administered to children 6 through 18 years of age who are at increased risk for invasive pneumococcal disease* (and no prior PCV13 doses)– Functional or anatomic asplenia, including sickle cell disease– HIV infection and other immunocompromising conditions– Cochlear implant– CSF leak

Regardless of previous history of PCV7 or PPSV vaccine

ACIP Recommendations for PCV13 Dose

*Off-label recommendation, ACIP vote, February 20, 2013

PCV13 Use in Adults

Licensed for use among adults >50 years old on 12/30/11

FDA approved under the Accelerated Approval Pathway

Based on noninferior immunogenicity compared to PPSV23

Postapproval condition of licensure: – Randomized controlled trial of PCV13 against pneumococcal pneumonia among

adults >65 years old in the Netherlands

PCV13 for Adults

ACIP now recommends PCV13 for adults 65 years old and older

Some adults have received PCV13 already

PCV13 for Adults (2014)

Incidence of IPD in Adults Aged 18-64 Years with Selected Underlying Conditions, United States, 2009

8

26 28 3241

5259

173186

0

20

40

60

80

100

120

140

160

180

200

HEALTHY CVD DIABETES PULMONARY KIDNEY LIVER ALCOHOL HIV/AIDSHEMATOLGICALCANCER

Cas

es p

er 1

00,0

00 p

erso

ns

3-7 fold increased risk

20 fold increased risk

Unpublished data, Active Bacterial Core surveillance, 2009

HEMATOLOGICAL CANCER

Adults 19 years of age or older with: – Immunocompromising conditions– Functional or anatomic asplenia– CSF leaks – Cochlear implants

Those who have not previously received PCV13 or PPSV23 should receive a single dose of PCV13 followed by a dose of PPSV23 at least 8 weeks later, with a booster dose of PPSV23 5 or more years later

PCV13 for Immunocompromised Adults*

*MMWR. October 12, 2012 ; 61(40):816-819

PPSV23 Use in Children and Adults

Persons 2 years and older with normal immune systems who have chronic illness including:

Persons in environments or settings with increased risk

Pneumococcal Polysaccharide Vaccine Recommendations

Cardiovascular disease Alcoholism

Pulmonary disease (asthma if 19 years old or older)

Smoking (19 years old or older)

Diabetes CSF leak

Liver disease Cochlear implant

Persons 2 years and older who are immunocompromised (due to disease or treatment)– Asplenia (functional or anatomic)– Chronic renal failure– Nephrotic syndrome – Hodgkin disease– Lymphoma and leukemia– Multiple myeloma– Organ transplant– HIV infection

Pneumococcal Polysaccharide Vaccine Recommendations

Routine revaccination of immunocompetent persons is not recommended

Revaccination recommended for persons 2-64 years of age who are at highest risk of serious pneumococcal infection

Pneumococcal Polysaccharide Vaccine Revaccination

MMWR 2010;59(No.34):1102-5

5-year interval (2-64 years) with additional dose after 65th birthday, 5 years after previous dose:– Functional or anatomic asplenia (including sickle cell disease)– Immunosuppression (including HIV infection)– Transplant– Chronic renal failure– Nephrotic syndrome

1 dose is recommended after the 65th birthday, but only 1 dose recommended after 65th birthday

Pneumococcal Polysaccharide VaccineCandidates for Revaccination

MMWR 2010;59(No.34):1102-5 and 2010;59(RR-11)

PCV13 and PPSV23 should not be administered during the same clinic visit – Either vaccine may be administered simultaneously with influenza vaccine

Administer PCV13 before PPSV23 whenever possible

Administering PCV13 and PPSV23 VaccinesGeneral Rules

www.cdc.gov/vaccines/vpd-vac/pneumo/downloads/adult-vax-clinician-aid.pdf

CDC Pneumococcal Vaccine Timing For Adults

http://www.cdc.gov/vaccines/vpd-vac/pneumo/downloads/adult-vax-clinician-aid.pdf

PCV13 and PPSV23 for Adults 19 – 64 Years

Immunocompromised, asplenic (sickle cell, hemoglobinopathy), CSF leaks, cochlear implants who are pneumococcal-naive

>8 weeks

PCV13 PPSV23+ + PPSV23* PPSV23(@ >65 years)+

>5 years >5 years

*Second PPSV23 dose before age 65 years NOT recommended for adults with CSF leaks or those with cochlear implants*ACIP off-label recommendation for PCV13 for adults 19 through 49 years of age

PCV13 and PPSV23 for Adults 19 – 64 Years

Immunocompromised, asplenic (sickle cell, hemoglobinopathy), CSF leaks, cochlear implants

who have previously received PPSV23

>1 year

PPSV23 PCV13+ + PPSV23* PPSV23(@ >65 years)+

>8 weeks >5 years

*Second PPSV23 dose before age 65 years NOT recommended for adults with CSF leaks or those with cochlear implants*ACIP off-label recommendation for PCV13 for adults 19 through 49 years of age

>5 years

PCV13 and PPSV23 for Adults 65 Years and Older

Pneumococcal-naïve or unknown vaccination historyHealthy adult

12 months

PCV13(@ >65 years) PPSV23+

If PPSV23 cannot be given at 12 months later, it should be given during the next visit

PCV13 and PPSV23 for Adults 65 Years and Older

Pneumococcal-naïve or unknown vaccination historyHigh-risk immunocompromised adult

8 weeks

PCV13(@ >65 years) PPSV23+

PCV13 and PPSV23 for Adults 65 Years and Older

Previously received 1 or more doses of PPSV23High-risk immunocompromised adult

> 1 year

PPSV23*(@ > 65 years)

PCV13+

PPSV23*(@ < 65 years) + PCV13

(@ > 65 years)PPSV23*

(@ > 65 years)+

> 1 year > 8 weeks

> 5 years*Doses already administered

Severe allergic reaction to vaccine component or following prior dose of vaccine

Moderate or severe acute illness

Pneumococcal VaccinesContraindications and Precautions

Administer PCV13 vaccine via intramuscular (IM) injection– Needle gauge: 22–25 gauge– Needle length*: 5/8 – 1.5 inch depending on the patient’s age and/or weight – Site*:

• Birth–11 months: Vastus lateralis muscle is preferred• 1–2 years: Vastus lateralis muscle is preferred; deltoid muscle may be used if the

muscle mass is adequate • 3 years and older: Deltoid muscle is preferred; vastus lateralis muscle may be

used

Administer at the same medical visit as other vaccines, except Men ACWY-D in asplenic persons (others, OK to administer)

Pneumococcal Conjugate (PCV13)Vaccine Administration

*Professional judgement should be used to determine the proper needle length and site. Factors influencing site including local reaction, number of vaccine to be administered age and muscle mass

PPSV23 maybe be administered by IM or subcutaneous injection – IM injection

• Needle gauge: 22–25 gauge• Needle length*: 1–1.5 inch depending on the patient’s age and/or weight • 2 years: Vastus lateralis muscle is preferred; deltoid muscle may be used if the

muscle mass is adequate • 3 years and older: Deltoid muscle is preferred; vastus lateralis muscle may be

used– Subcutaneous injection:

• Needle gauge/length: 23–25 gauge; 5/8th inch needle in the upper outer triceps area

Vaccine AdministrationPPSV23

*Professional judgement should be used to determine the proper needle length and site. Influencing factors include injection technique, local reaction, number of vaccines to be administered, patient age, size and muscle mass

PPSV23 PCV

Local reactions 30%-50% 5%-49%

Fever, myalgia <1% 24-35%

Febrile seizures --- Rare: 1-14/100,000; with IIV 4 -45/ 100,000

Severe adverse reactions rare 8% (local)

Pneumococcal Vaccines Adverse Reactions